Pablo Eiras - Academia.edu (original) (raw)

Papers by Pablo Eiras

Research paper thumbnail of Lost in the system: identification of patients with undiagnosed primary biliary cholangitis

Journal of Hepatology, 2020

Research paper thumbnail of Intraepithelial lymphocyte immunophenotype: a useful tool in the diagnosis of celiac disease

Journal of Physiology and Biochemistry, 2017

According to new ESPGHAN guidelines, gluten challenge is considered necessary when there is doubt... more According to new ESPGHAN guidelines, gluten challenge is considered necessary when there is doubt about the initial diagnosis of celiac disease (CD). The main aim of this study was to quantify intraepithelial lymphocyte (IEL) immunophenotype on celiac patients on gluten-containing diet (GCD) compared to those on gluten-free diet (GFD). Another aim was to evaluate the clinical utility of IELs in the CD diagnosis, especially in selected patients on GFD where diagnostic uncertainty remains. IEL immunophenotype (TCRγδ and NK-like IELs) were studied by flow cytometry in 111 children with CD (81 children with CD on GCD and 30 celiac patients on GFD) and a control group (10 children). Duration of GFD was 5.4 ± 1.6 years. TCRγδ IELs in celiac patients receiving a GCD or GFD were significantly higher (p < 0.001) than in the control group. NK-like IELs in patients receiving a GCD or GFD were significantly lower than in the control group (p < 0.001). We observed a permanent decrease of NK-like IELs and an increment of TCRγδ IELs after following an adequate establishment and compliance of a longterm GFD in celiac patients. Recognition of IELs changes in the intestinal mucosa on celiac patients after long-term establishment of a GFD could constitute a useful tool for CD diagnosis in various situations: in which there is doubt about the initial diagnosis and repeat biopsy is necessary (avoiding the need of gluten challenges), and in those patients with symptoms/signs suggestive of CD who maintain a low gluten diet.

Research paper thumbnail of Anticuerpos anticitoplasma de neutr�filo: otras especificidades antig�nicas

Research paper thumbnail of Specificity of IEL Profiling in the Diagnosis of Celiac Disease

The American Journal of Gastroenterology, 2004

TO THE EDITOR: We read with interest the recent article by Jarvinen et al. ( 1 ). This article de... more TO THE EDITOR: We read with interest the recent article by Jarvinen et al. ( 1 ). This article describes the changes in intraepithelial lymphocytes (IEL) subsets observed in a vast series of patients. ... To read this article in full you may need to log in, make a payment or gain ...

Research paper thumbnail of Flow cytometry description of a novel CD3?/CD7+ intraepithelial lymphocyte subset in human duodenal biopsies: Potential diagnostic value in coeliac disease

Cytometry, 1998

Intraepithelial lymphocytes (IEL) represent a heterogeneous cellular compartment of unknown funct... more Intraepithelial lymphocytes (IEL) represent a heterogeneous cellular compartment of unknown functions and controversial ontogeny. Previous observations in humans indicate that the majority of IEL subsets express the CD3 complex associated with either the alphabeta or the gammadelta T-cell receptor components, and describe the characteristic increase of CD3+TCRgammadelta+ IEL in coeliac disease. In the present work, we analyze the surface antigen expression of intraepithelial lymphocytes isolated from duodenal biopsies of control subjects and coeliac disease patients. We describe a CD3-CD7 + IEL subset frequently found in control subjects (41.41+/-21.8), with the following features: 1) most of these cells are CD45R0+ CD103+ and CD44- CD28- CD5-; 2) a significant percentage express CD56 (44.7%+/-21.3), CD2 (55.1%+/-16.2), and CD94 (16.2%+/-7.3). Furthermore, they are CD122+ and CD25-; 3) this CD3- IEL subset exhibit an activated phenotype expressing higher levels of CD69, CD103, and CD38 than the CD3+ subset. Interestingly, this CD3- subset is drastically reduced in CD patients (2.2+/-2.9 in active disease, 6.3+/-4.6 in treated patients versus 41.4+/-21.8 in control subjects). The imbalanced ratio &quot;increased TCRgammadelta versus decreased CD3- CD7+&quot; is a permanent finding in CD patients following clinical and histological remission. This parameter might provide helpful diagnostic information (easily obtained by 3-color FCM from diagnostic biopsies), and suggest a potential implication in the pathogenesis of coeliac disease.

Research paper thumbnail of Origin and immunophenotype of intestinal intraepithelial lymphocytes in experimental long-surviving small bowel allografts

Transplantation Proceedings, 2002

Research paper thumbnail of Limitations of anti-guinea pig liver transglutaminase IgA in screening of celiac disease

Research paper thumbnail of CD106 and activated-CD29 are expressed on myelomatous bone marrow plasma cells and their downregulation is associated with tumour progression

British Journal of Haematology, 2002

Research paper thumbnail of Mechanistic Aspects of the Induction of Apoptosis by Lauryl Gallate in the Murine B-Cell Lymphoma Line Wehi 231

Archives of Biochemistry and Biophysics, 2000

The effect of lauryl gallate (antioxidant E-312) has been studied on the mouse B-cell lymphoma li... more The effect of lauryl gallate (antioxidant E-312) has been studied on the mouse B-cell lymphoma line Wehi 231. This compound is able to inhibit protein tyrosine kinases (PTKs) in whole cells and in crude extracts with a better efficiency than other well-known PTK inhibitors such as herbimycin or genistein. Initial events triggered upon the incubation of cells with lauryl gallate in phosphate-buffered saline (up to 1 h) include the inhibition of tyrosine phosphorylation, discharge of the mitochondrial transmembrane potential, and induction of mRNA for Bcl-2. Long-term cultures in complete medium supplemented with fetal calf serum (up to 24 h) in the presence of this compound exhibit clear apoptotic features such as increase in phosphatidylserine in the cell surface, decrease in the functionality of mitochondria, cytochrome c release to the cytosol, activation of caspases, hypodiploidy, and oligonucleosomal breakdown of DNA. Comparison between Wehi cells overexpressing Bcl-2 (Wehi-bcl-2) with Wehi-neo cells shows a delay in the manifestations of the apoptotic signs, indicating that Bcl-2 has a partial protective effect on the apoptosis induced by lauryl gallate. The proapoptotic effect of lauryl gallate is not dependent on DNA or protein synthesis, is not blocked by the chelation of calcium, and is not reverted by N-acetylcysteine.

Research paper thumbnail of Carrot-induced asthma: Immunodetection of allergens

Journal of Allergy and Clinical Immunology, 1997

Daucus carota L. (carrot) is a vegetable that belongs to Umbelliferae family (Apiaceae). It is fr... more Daucus carota L. (carrot) is a vegetable that belongs to Umbelliferae family (Apiaceae). It is frequently implicated in food allergy and oral allergy syndrome, usually in association with other foods. Thus, hypersensitivity to carrot is commonly associated with allergy to Apiaceae species and sensitization to birch and mugwort pollens [1,2]. In this sense, it is important to note that in southern Spain, allergy to Artemisa vulgaris is quite frequent, in contrast to what happens with Betula verrucosa. Nevertheless, few cases of rhinitis and asthma induced by carrot allergy have been described [3,4]. This investigation was carried out to study the involved allergens in a case of occupational rhino-conjunctivitis by carrot. We report the case of a 38-years-old cook man, diagnosed from allergic rhinitis and asthma due to mite and pollen that had been treated successfully with subcutaneous immunotherapy. For the previous 3 years, the patient had been presented facial contact urticaria, sneezing, rhinorrhea and conjunctivitis symptoms within few minutes of handling or cutting raw carrots, although he had been tolerated its raw and cooked intake. Skin prick test (SPT) was done with a set of airborne and commercial food allergens, as well as native fresh foods. The result of SPT was positive (wheal average diameter ≥ 3 mm) to house dust mite, cat, dog, and pollens from grasses, Salsola and Olea; and negative to Artemisia and birch pollens, LTP, profilin, and commercial extract of carrot. Native fresh food

Research paper thumbnail of Anticuerpos anticitoplasma de neutrófilo: otras especificidades antigénicas

Seminarios de la Fundación Española de Reumatología, 2008

The value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of several types of i... more The value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of several types of idiopathic vasculitis is well-documented: in these diseases, ANCA show two classic immunofluorescence patterns (C-ANCA and P-ANCA), which are directed against myeloperoxidase and proteinase-3, respectively. However, in recent years, new ANCA antigens have been discovered, showing atypical immunofluorescence patterns in patients with diverse diseases and clinical conditions. This review attempts to summarize the clinical value of determining these autoantibodies and their role in the study of the diseases in which they most frequently appear.

Research paper thumbnail of Intraepithelial lymphocytes and coeliac disease: permanent changes in CD3-/CD7+ and T cell receptor ?-d subsets studied by flow cytometry

Acta Paediatrica, 2000

Permanent changes in intestinal intraepithelial lymphocytes have been observed in coeliac patient... more Permanent changes in intestinal intraepithelial lymphocytes have been observed in coeliac patients. The aim of this investigation was to study small intestinal intraepithelial lymphocytes by using flow cytometry and to evaluate its diagnostic value in coeliac disease. Three-colour flow cytometry analyses were performed on isolated epithelial cells of 117 intestinal biopsies obtained from 113 children (54 coeliac disease, 4 other enteropathies, 18 Helicobacter pylori associated gastritis and 37 normal controls). A multiple logistic regression model was developed to select the best intraepithelial lymphocytes subset predictor of coeliac disease. Coeliac patients had significant higher levels of T cell receptor gammadelta intraepithelial lymphocytes than control patients (p &lt; 0.01), H. pylori patients (p &lt; 0.01) and other enteropathies (p &lt; 0.05). The density of CD3-/CD7+ intraepithelial lymphocytes, a intraepithelial lymphocyte subset poorly characterized by immunohistochemical methods, was significantly lower in coeliac patients than in the control group (p &lt; 0.01). H. pylori group (p &lt; 0.01) and other enteropathies (p &lt; 0.01). Both changes remained altered independent of the coeliac patient&#39;s diet. The data were used on a logistic regression analysis in order to calculate sensitivity [94.4%; 95% confidence interval (CI) 83.7-98.6%], specificity (94.9%; 95% CI 84.9-98.7%) and likelihood ratio for a positive test 18.5 (95% CI 6.1-55.8) in the diagnosis of coeliac disease. Changes in T cell receptor gammadelta and CD3-/CD7+ intraepithelial lymphocytes subsets are permanently observed in paediatric coeliac disease. Their assessment, by three-colour flow cytometry on routine diagnostic biopsies, permits a better characterization of coeliac enteropathy and represents a valuable procedure to identify coeliac patients with different clinical presentations.

Research paper thumbnail of Lost in the system: identification of patients with undiagnosed primary biliary cholangitis

Journal of Hepatology, 2020

Research paper thumbnail of Intraepithelial lymphocyte immunophenotype: a useful tool in the diagnosis of celiac disease

Journal of Physiology and Biochemistry, 2017

According to new ESPGHAN guidelines, gluten challenge is considered necessary when there is doubt... more According to new ESPGHAN guidelines, gluten challenge is considered necessary when there is doubt about the initial diagnosis of celiac disease (CD). The main aim of this study was to quantify intraepithelial lymphocyte (IEL) immunophenotype on celiac patients on gluten-containing diet (GCD) compared to those on gluten-free diet (GFD). Another aim was to evaluate the clinical utility of IELs in the CD diagnosis, especially in selected patients on GFD where diagnostic uncertainty remains. IEL immunophenotype (TCRγδ and NK-like IELs) were studied by flow cytometry in 111 children with CD (81 children with CD on GCD and 30 celiac patients on GFD) and a control group (10 children). Duration of GFD was 5.4 ± 1.6 years. TCRγδ IELs in celiac patients receiving a GCD or GFD were significantly higher (p < 0.001) than in the control group. NK-like IELs in patients receiving a GCD or GFD were significantly lower than in the control group (p < 0.001). We observed a permanent decrease of NK-like IELs and an increment of TCRγδ IELs after following an adequate establishment and compliance of a longterm GFD in celiac patients. Recognition of IELs changes in the intestinal mucosa on celiac patients after long-term establishment of a GFD could constitute a useful tool for CD diagnosis in various situations: in which there is doubt about the initial diagnosis and repeat biopsy is necessary (avoiding the need of gluten challenges), and in those patients with symptoms/signs suggestive of CD who maintain a low gluten diet.

Research paper thumbnail of Anticuerpos anticitoplasma de neutr�filo: otras especificidades antig�nicas

Research paper thumbnail of Specificity of IEL Profiling in the Diagnosis of Celiac Disease

The American Journal of Gastroenterology, 2004

TO THE EDITOR: We read with interest the recent article by Jarvinen et al. ( 1 ). This article de... more TO THE EDITOR: We read with interest the recent article by Jarvinen et al. ( 1 ). This article describes the changes in intraepithelial lymphocytes (IEL) subsets observed in a vast series of patients. ... To read this article in full you may need to log in, make a payment or gain ...

Research paper thumbnail of Flow cytometry description of a novel CD3?/CD7+ intraepithelial lymphocyte subset in human duodenal biopsies: Potential diagnostic value in coeliac disease

Cytometry, 1998

Intraepithelial lymphocytes (IEL) represent a heterogeneous cellular compartment of unknown funct... more Intraepithelial lymphocytes (IEL) represent a heterogeneous cellular compartment of unknown functions and controversial ontogeny. Previous observations in humans indicate that the majority of IEL subsets express the CD3 complex associated with either the alphabeta or the gammadelta T-cell receptor components, and describe the characteristic increase of CD3+TCRgammadelta+ IEL in coeliac disease. In the present work, we analyze the surface antigen expression of intraepithelial lymphocytes isolated from duodenal biopsies of control subjects and coeliac disease patients. We describe a CD3-CD7 + IEL subset frequently found in control subjects (41.41+/-21.8), with the following features: 1) most of these cells are CD45R0+ CD103+ and CD44- CD28- CD5-; 2) a significant percentage express CD56 (44.7%+/-21.3), CD2 (55.1%+/-16.2), and CD94 (16.2%+/-7.3). Furthermore, they are CD122+ and CD25-; 3) this CD3- IEL subset exhibit an activated phenotype expressing higher levels of CD69, CD103, and CD38 than the CD3+ subset. Interestingly, this CD3- subset is drastically reduced in CD patients (2.2+/-2.9 in active disease, 6.3+/-4.6 in treated patients versus 41.4+/-21.8 in control subjects). The imbalanced ratio &quot;increased TCRgammadelta versus decreased CD3- CD7+&quot; is a permanent finding in CD patients following clinical and histological remission. This parameter might provide helpful diagnostic information (easily obtained by 3-color FCM from diagnostic biopsies), and suggest a potential implication in the pathogenesis of coeliac disease.

Research paper thumbnail of Origin and immunophenotype of intestinal intraepithelial lymphocytes in experimental long-surviving small bowel allografts

Transplantation Proceedings, 2002

Research paper thumbnail of Limitations of anti-guinea pig liver transglutaminase IgA in screening of celiac disease

Research paper thumbnail of CD106 and activated-CD29 are expressed on myelomatous bone marrow plasma cells and their downregulation is associated with tumour progression

British Journal of Haematology, 2002

Research paper thumbnail of Mechanistic Aspects of the Induction of Apoptosis by Lauryl Gallate in the Murine B-Cell Lymphoma Line Wehi 231

Archives of Biochemistry and Biophysics, 2000

The effect of lauryl gallate (antioxidant E-312) has been studied on the mouse B-cell lymphoma li... more The effect of lauryl gallate (antioxidant E-312) has been studied on the mouse B-cell lymphoma line Wehi 231. This compound is able to inhibit protein tyrosine kinases (PTKs) in whole cells and in crude extracts with a better efficiency than other well-known PTK inhibitors such as herbimycin or genistein. Initial events triggered upon the incubation of cells with lauryl gallate in phosphate-buffered saline (up to 1 h) include the inhibition of tyrosine phosphorylation, discharge of the mitochondrial transmembrane potential, and induction of mRNA for Bcl-2. Long-term cultures in complete medium supplemented with fetal calf serum (up to 24 h) in the presence of this compound exhibit clear apoptotic features such as increase in phosphatidylserine in the cell surface, decrease in the functionality of mitochondria, cytochrome c release to the cytosol, activation of caspases, hypodiploidy, and oligonucleosomal breakdown of DNA. Comparison between Wehi cells overexpressing Bcl-2 (Wehi-bcl-2) with Wehi-neo cells shows a delay in the manifestations of the apoptotic signs, indicating that Bcl-2 has a partial protective effect on the apoptosis induced by lauryl gallate. The proapoptotic effect of lauryl gallate is not dependent on DNA or protein synthesis, is not blocked by the chelation of calcium, and is not reverted by N-acetylcysteine.

Research paper thumbnail of Carrot-induced asthma: Immunodetection of allergens

Journal of Allergy and Clinical Immunology, 1997

Daucus carota L. (carrot) is a vegetable that belongs to Umbelliferae family (Apiaceae). It is fr... more Daucus carota L. (carrot) is a vegetable that belongs to Umbelliferae family (Apiaceae). It is frequently implicated in food allergy and oral allergy syndrome, usually in association with other foods. Thus, hypersensitivity to carrot is commonly associated with allergy to Apiaceae species and sensitization to birch and mugwort pollens [1,2]. In this sense, it is important to note that in southern Spain, allergy to Artemisa vulgaris is quite frequent, in contrast to what happens with Betula verrucosa. Nevertheless, few cases of rhinitis and asthma induced by carrot allergy have been described [3,4]. This investigation was carried out to study the involved allergens in a case of occupational rhino-conjunctivitis by carrot. We report the case of a 38-years-old cook man, diagnosed from allergic rhinitis and asthma due to mite and pollen that had been treated successfully with subcutaneous immunotherapy. For the previous 3 years, the patient had been presented facial contact urticaria, sneezing, rhinorrhea and conjunctivitis symptoms within few minutes of handling or cutting raw carrots, although he had been tolerated its raw and cooked intake. Skin prick test (SPT) was done with a set of airborne and commercial food allergens, as well as native fresh foods. The result of SPT was positive (wheal average diameter ≥ 3 mm) to house dust mite, cat, dog, and pollens from grasses, Salsola and Olea; and negative to Artemisia and birch pollens, LTP, profilin, and commercial extract of carrot. Native fresh food

Research paper thumbnail of Anticuerpos anticitoplasma de neutrófilo: otras especificidades antigénicas

Seminarios de la Fundación Española de Reumatología, 2008

The value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of several types of i... more The value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of several types of idiopathic vasculitis is well-documented: in these diseases, ANCA show two classic immunofluorescence patterns (C-ANCA and P-ANCA), which are directed against myeloperoxidase and proteinase-3, respectively. However, in recent years, new ANCA antigens have been discovered, showing atypical immunofluorescence patterns in patients with diverse diseases and clinical conditions. This review attempts to summarize the clinical value of determining these autoantibodies and their role in the study of the diseases in which they most frequently appear.

Research paper thumbnail of Intraepithelial lymphocytes and coeliac disease: permanent changes in CD3-/CD7+ and T cell receptor ?-d subsets studied by flow cytometry

Acta Paediatrica, 2000

Permanent changes in intestinal intraepithelial lymphocytes have been observed in coeliac patient... more Permanent changes in intestinal intraepithelial lymphocytes have been observed in coeliac patients. The aim of this investigation was to study small intestinal intraepithelial lymphocytes by using flow cytometry and to evaluate its diagnostic value in coeliac disease. Three-colour flow cytometry analyses were performed on isolated epithelial cells of 117 intestinal biopsies obtained from 113 children (54 coeliac disease, 4 other enteropathies, 18 Helicobacter pylori associated gastritis and 37 normal controls). A multiple logistic regression model was developed to select the best intraepithelial lymphocytes subset predictor of coeliac disease. Coeliac patients had significant higher levels of T cell receptor gammadelta intraepithelial lymphocytes than control patients (p &lt; 0.01), H. pylori patients (p &lt; 0.01) and other enteropathies (p &lt; 0.05). The density of CD3-/CD7+ intraepithelial lymphocytes, a intraepithelial lymphocyte subset poorly characterized by immunohistochemical methods, was significantly lower in coeliac patients than in the control group (p &lt; 0.01). H. pylori group (p &lt; 0.01) and other enteropathies (p &lt; 0.01). Both changes remained altered independent of the coeliac patient&#39;s diet. The data were used on a logistic regression analysis in order to calculate sensitivity [94.4%; 95% confidence interval (CI) 83.7-98.6%], specificity (94.9%; 95% CI 84.9-98.7%) and likelihood ratio for a positive test 18.5 (95% CI 6.1-55.8) in the diagnosis of coeliac disease. Changes in T cell receptor gammadelta and CD3-/CD7+ intraepithelial lymphocytes subsets are permanently observed in paediatric coeliac disease. Their assessment, by three-colour flow cytometry on routine diagnostic biopsies, permits a better characterization of coeliac enteropathy and represents a valuable procedure to identify coeliac patients with different clinical presentations.